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Effect of association of cellular therapy and low-intensity training on MDX mouse dystrophic muscle

Grant number: 18/11752-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2018
Effective date (End): March 31, 2021
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Carlos Eduardo Ambrósio
Grantee:Priscilla Avelino Ferreira Pinto
Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil

Abstract

Duchenne Muscular Dystrophy is a genetic disease, characterized by the total absence of the of dystrophin protein, which leads to progressive muscular degeneration and chronic inflammatory process. Advances in cell therapy have been performed, however, cell viability has been limited by the presence of muscle fibrosis and inflammatory process. Another therapy used has been the Low-Intensity physical Training (LIT), being able to reduce inflammatory process and muscular fibrosis. Thus, this study aims to evaluate the effect of the association of cell therapy with LIT on the dystrophic muscle of MDX mice. The project will be carried out in three stages. Step 1: A mesoangioblasts cell culture (MAB) protocol derived from the canine yolk sac and compared to muscle derived MAB will be developed. Step 2: The viability of stem cells will be evaluated in vivo, with application in mdx and wild-type mice. Step 3: Cell therapy and LIT performed in a horizontal treadmill in mdx mice will be associated. Functional tests are performed and at the end of the therapeutic protocol the animals will be euthanized and the tibial cranial, gastrocnemius, diaphragm and heart muscles will be dissected. Histological and histomorphometric analysis, muscular dystrophin analysis by immunohistochemistry and gene expression by RT-qPCR will be performed. In addition, we will perform analysis of inflammatory cytokines by ELISA method and gene expression of markers linked to muscle regeneration and inflammatory cytokines by RT-qPCR. The results will be analyzed by descriptive statistics and comparative tests of group means. (AU)